rs752705562

Variant names:

• chr7-23684573-C-A
• rs752705562
• NM_199136.5:c.140C>A

Your query was ambiguous. Multiple possible variants found:

• chr7-23684573-C-A
• chr7-23684573-C-G
• chr7-23684573-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_199136.5(FAM221A):​c.140C>A​(p.Pro47His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,748 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P47L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: FAM221A NM_199136.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.62
• Publications: 0 publications found

Genes affected

FAM221A (HGNC:27977): (family with sequence similarity 221 member A)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_199136.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM221A	NM_199136.5	MANE Select	c.140C>A	p.Pro47His	missense	Exon 2 of 7	NP_954587.2	A4D161-1
	FAM221A	NM_001127364.3		c.140C>A	p.Pro47His	missense	Exon 2 of 6	NP_001120836.1	A4D161-2
	FAM221A	NM_001300932.2		c.65+4290C>A		intron	N/A	NP_001287861.1	B8ZZQ8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM221A	ENST00000344962.9	TSL:1 MANE Select	c.140C>A	p.Pro47His	missense	Exon 2 of 7	ENSP00000342576.4	A4D161-1
	FAM221A	ENST00000409192.7	TSL:1	c.140C>A	p.Pro47His	missense	Exon 2 of 6	ENSP00000386927.3	A4D161-2
	FAM221A	ENST00000409994.3	TSL:1	c.65+4290C>A		intron	N/A	ENSP00000386631.3	A4D161-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461748 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 727172

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 86238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1111940

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.065	T
Eigen	Pathogenic	0.88
Eigen_PC	Pathogenic	0.83
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.050	D
MetaRNN	Uncertain	0.67	D
MetaSVM	Benign	-0.73	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		7.6
PrimateAI	Uncertain	0.59	T
PROVEAN	Pathogenic	-4.8	D
REVEL	Uncertain	0.52
Sift	Uncertain	0.0020	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.61
MutPred		0.32		Gain of helix (P = 0.0117)
MVP		0.26
MPC		0.46
ClinPred		1.0	D
GERP RS		5.4
Varity_R		0.60
gMVP		0.62
Mutation Taster		=16/84	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs752705562; hg19: chr7-23724192; COSMIC: COSV61387743; COSMIC: COSV61387743;